The objective of this research program is to contribute to an understanding of the molecular basis of metabolic events that involve enzymes attached to intracellular membranes. Initially, the electron transport sequence of liver endoplasmic reticulum which catalyzes the NADH and oxygen dependent desaturation of stearyl-CoA will be examined. The primary and tertiary structures of two purified enzyme components, cytochrome b5 and cytochrome b5 reductase, will be examined further by sequencing techniques, and spectral, fluorescence, and chemical methods to identify essential structural features related to catalysis and to membrane attachment. A third enzyme, stearyl-CoA desaturase, will be subjected to similar characterization after purification. Lipid vesicle preparations will be used to examine the structural specificity of lipid bilayers for binding these enzymes, and attempts will be made to describe the spatial relationships and mobilities of these proteins when bound to lipid bilayers by utilizing fluorescence, NMR and immunologic techniques. These, and subsequent studies on related microsomal enzymes, should help to define the spectrum of lipid-protein interactions that regulate catalytic or other functions of proteins of various biomembranes, and thereby add to a general appreciation of the subtle relations between membrane structure and function.